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Title: Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.
Authors: Hancock, Dana B.
Soler Artigas, Maria
Gharib, Sina A.
Henry, Amanda
Manichaikul, Ani
Ramasamy, Adaikalavan
Loth, Daan W.
Imboden, Medea
Koch, Beate
McArdle, Wendy L.
Smith, Albert V.
Smolonska, Joanna
Sood, Akshay
Tang, Wenbo
Wilk, Jemma B.
Zhai, Guangju
Zhao, Jing Hua
Aschard, Hugues
Burkart, Kristin M.
Curjuric, Ivan
Eijgelsheim, Mark
Elliott, Paul
Gu, Xiangjun
Harris, Tamara B.
Janson, Christer
Homuth, Georg
Hysi, Pirro G.
Liu, Jason Z.
Loehr, Laura R.
Lohman, Kurt
Loos, Rurth J.F.
Manning, Alisa K.
Marciante, Kristin D.
Obeidat, Ma'en
Postma, Dirkje S.
Aldrich, Melinda C.
Brusselle, Guy G.
Chen, Ting-Hsu
Eiriksdottir, Gudny
Franceschini, Nora
Heinrich, Joachim
Rotter, Jerome I.
Wijmenga, Cisca
Williams, O. Dale
Bentley, Amy R.
Hofman, Albert
Laurie, Cathy C.
Lumley, Thomas
Morrison, Alanna C.
Joubert, Bonnie R.
Rivadeneira, Fernando
Couper, David J.
Kritchevsky, Stephen B.
Liu, Yongmei
Wjst, Matthias
Wain, Louise V.
Vonk, Judith M.
Uitterlinden, André G.
Rochat, Thierry
Rich, Stephen S.
Psaty, Bruce M.
O'Connor, George T.
North, Karl E.
Mirel, Daniel B.
Meibohm, Bernd
Launer, Lenore J.
Khaw, Kay-Tee
Hartikainen, Anna-Liisa
Hammond, Christopher J.
Gläser, Sven
Marchini, Jonathan
Kraft, Peter
Wareham, Nicholas J.
Völzke, Henry
Stricker, Bruno H.C.
Spector, Timothy D.
Probst-Hensch, Nicole M.
Jarvis, Deborah
Jarvelin, Marjo-Riitta
Heckbert, Susan R.
Gudnason, Vilmundur
Boezen, H. Marike
Barr, R. Graham
Cassano, Patricia A.
Strachan, David P.
Fornage, Myriam
Hall, Ian P.
Dupuis, Josée
Tobin, Martin D.
London, Stephanie J.
First Published: 20-Dec-2012
Publisher: Public Library of Science
Citation: PLoS Genet, 2012, 8 (12), e1003098.
Abstract: Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1)), and its ratio to forced vital capacity (FEV(1)/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV(1) and FEV(1)/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = )5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMA = )4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMA = )1.28×10(-8)) were associated with FEV(1)/FVC or FEV(1) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.
DOI Link: 10.1371/journal.pgen.1003098
ISSN: 1553-7390
eISSN: 1553-7404
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Appears in Collections:Published Articles, Dept. of Health Sciences

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